Project description
The determinants of metabolic health – the role of inflammation
Obesity is known to cause various metabolic comorbidities, such as diabetes. Although inflammation is a key driver of metabolic diseases, anti-inflammatory drugs have not shown any therapeutic efficacy. The MATRIX is an EU-funded project that is investigating the differences between metabolically healthy and unhealthy individuals. Scientists are working under the hypothesis that the ability to resolve inflammation and not pro-inflammation is what differentiates the two states. Using cutting-edge techniques, scientists will focus on adipose extracellular-matrix remodelling mechanisms and evaluate the therapeutic potential of pro-resolving lipids in patient-derived cell lines. Results may lead to a novel approach to tackle obesity-related pathologies.
Objective
                                Obesity and its affiliated metabolic diseases pose serious public-health challenges. However, certain patient subgroups appear protected. To halt the socio-economic burden of metabolic disease, we urgently need to understand what distinguishes the Metabolically-Healthy-Lean (MHL), Metabolically-Unhealthy-Lean (MUL), Metabolically-Healthy-Obese (MHO) and Metabolically-Unhealthy-Obese (MUO) phenotypes, and which factors promote metabolic health. Inflammation has been proposed as a target, as it is a key driver of metabolic disease. However, clinical trials show limited evidence that anti-inflammatory drugs reduce diabetes. Why is that? 
Inflammation consists of a pro-inflammatory phase followed by a pro-resolving phase, which are regulated by different cells/pathways. This is critical to consider when attempting a therapeutic approach. Based on my preliminary data, I hypothesise that what separates MHL/MHO from MUL/MUO are not pro-inflammatory triggers, but rather the endogenous ability of individuals to resolve inflammation. Adipose extracellular-matrix remodelling appears critical, and pro-resolving lipids promote a MUO-to-MHO switch.
My overall goal is to determine molecular pathways that differentiate the MHL/MUL/MHO/MUO phenotypes (Aim 1-4), and to investigate the therapeutic potential of pro-resolving lipids (Aim 5). This multi-disciplinary project combines cutting-edge techniques with state-of-the-art translational approaches. Through my unique access to human biobanks, I will generate patient-specific cell-lines and test drug-targets ex vivo. Novel bioinformatics pipelines will produce protein/lipid/metabolite fingerprints associated with respective patient groups, ultimately providing a new approach to tackle obesity-related comorbidities. My experience in the specialised field of pro-resolving lipid biology, coupled with my lab’s unique placement at a translational site, makes me the right candidate to lead this research program.
                            
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                                                CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See:   The European Science Vocabulary.
                                                
                                            
                                        
                                                                                                
                            
                                                                                                CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
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                                        Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
                                        
                                    
                                
                            
                            
                        Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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                  H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
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ERC-STG - Starting Grant
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(opens in new window) ERC-2018-STG
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8000 Aarhus C
Denmark
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